Gamma-Aminobutyric acid (GABA) is an important inhibitory transmitter in the nervous systems of a variety of species. It is important in the regulation of neuronal excitability and in synaptic transmission. The applicant has developed a hypothesis that suggests the possibility that there may be a defect in the function of the GABA system in the brains of individuals who may have a predisposition to schizophrenia. It is proposed to begin the test of this hypothesis by studying the distribution and properties of the enzyme that forms GABA from glutamic acid in brain, L-glutamic acid decarboxylase (GAD). We plan to extend our work in areas dealing with genetic applications. These relate to studying the polymorphism of GAD in the brains of man and mouse and in nervous tissue of Drosophila. We also plan to continue investigation of CNS tissue of mice with hereditary neurological disorders and to begin work with brain tissue from mouse strains that are normal neurologically but differ behaviorally.